F2RL1 - Proteinase-activated receptor 2 - human protein (Function)
 
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F2RL1 »  Proteinase-activated receptor 2  (PAR-2)
 
Protein also known as:  Coagulation factor II receptor-like 1. Cleaved into:  Proteinase-activated receptor 2, alternate cleaved 1; Proteinase-activated receptor 2, alternate cleaved 2.
Gene name:  F2RL1
Entry whose protein(s) existence is based on evidence at protein level
extend overview
1 261 1
GENE REF ISO

Function

 show evidences
Overview 
Receptor for trypsin and trypsin-like enzymes coupled to G proteins. Its function is mediated through the activation of several signaling pathways including phospholipase C (PLC), intracellular calcium, mitogen-activated protein kinase (MAPK), I-kappaB kinase/NF-kappaB and Rho. Can also be transactivated by cleaved F2R/PAR1. Involved in modulation of inflammatory responses and regulation of innate and adaptive immunity, and acts as a sensor for proteolytic enzymes generated during infection. Generally is promoting inflammation. Can signal synergistically with TLR4 and probably TLR2 in inflammatory responses and modulates TLR3 signaling. Has a protective role in establishing the endothelial barrier; the activity involves coagulation factor X. Proposed to have a bronchoprotective role in airway epithelium, but also shown to compromise the airway epithelial barrier by interrupting E-cadherin adhesion. Involved in the regulation of vascular tone; activation results in hypotension presumably mediated by vasodilation. Associates with a subset of G proteins alpha subunits such as G alpha-q, G alpha-11, G alpha-14, G alpha-12 and G alpha-13, but probably not with G(o) alpha, G(i) subunit alpha-1 and G(i) subunit alpha-2. However, according to PubMed:21627585 can signal through G(i) subunit alpha. Believed to be a class B receptor which internalizes as a complex with arrestin and traffic with it to endosomal vesicles, presumably as desensitized receptor, for extended periods of time. Mediates inhibition of TNF-alpha stimulated JNK phosphorylation via coupling to G alpha-q/11; the function involves dissociation of RIPK1 and TRADD from TNFR1. Mediates phosphorylation of nuclear factor NF-kappa-B RELA subunit at 'Ser-536'; the function involves IKBKB and is predominantly independent of G proteins. Involved in cellular migration. Involved in cytoskeletal rearrangement and chemotaxis through beta-arrestin-promoted scaffolds; the function is independent of G alpha-q/11 and involves promotion of cofilin dephosphoryltaion and actin filament severing. Induces redistribution of COPS5 from the plasma membrane to the cytosol and activation of the JNK cascade is mediated by COPS5. Involved in the recruitment of leukocytes to the sites of inflammation and is the major PAR receptor capable of modulating eosinophil function such as proinflammatory cytokine secretion, superoxide production and degranulation. During inflammation promotes dendritic cell maturation, trafficking to the lymph nodes and subsequent T-cell activation. Involved in antimicrobial response of innate immnune cells; activation enhances phagocytosis of Gram-positive and killing of Gram-negative bacteria. Acts synergistically with interferon-gamma in enhancing antiviral responses. Implicated in a number of acute and chronic inflammatory diseases such as of the joints, lungs, brain, gastrointestinal tract, periodontium, skin, and vascular systems, and in autoimmune disorders.  
25
  • UniProtKB
GO molecular function 
G-protein alpha-subunit bindingdefinition[GO:0001965]  
1
  • Ortholog Curator
G-protein beta-subunit bindingdefinition[GO:0031681]  
1
  • Ortholog Curator
G-protein coupled receptor activitydefinition[GO:0004930]  
2
  • UniProtKB
  • Ortholog Curator
Protein bindingdefinition[GO:0005515]  
5
  • IntAct
Receptor activitydefinition[GO:0004872]  
1
  • PINC
Receptor bindingdefinition[GO:0005102]  
1
  • PINC
Thrombin receptor activitydefinition[GO:0015057] silver  
1
  • InterPro 2 GO
GO biological process 
Blood coagulationdefinition[GO:0007596] silver  
1
  • InterPro 2 GO
Chemokine (C-C motif) ligand 2 secretiondefinition[GO:0035926]  
1
  • UniProtKB
Chemokine secretiondefinition[GO:0090195]  
2
  • UniProtKB
Defense response to virusdefinition[GO:0051607]  
2
  • UniProtKB
Establishment of endothelial barrierdefinition[GO:0061028]  
1
  • UniProtKB
G-protein coupled receptor signaling pathwaydefinition[GO:0007186]  
1
  • PINC
Inflammatory responsedefinition[GO:0006954]  
1
  • UniProtKB KW
Innate immune responsedefinition[GO:0045087]  
1
  • UniProtKB KW
Interferon-gamma secretiondefinition[GO:0072643]  
1
  • Ortholog Curator
Interleukin-1 beta secretiondefinition[GO:0050702]  
1
  • UniProtKB
Interleukin-10 secretiondefinition[GO:0072608]  
1
  • UniProtKB
Leukocyte migrationdefinition[GO:0050900]  
1
  • UniProtKB
Leukocyte proliferationdefinition[GO:0070661]  
1
  • Ortholog Curator
Mature conventional dendritic cell differentiationdefinition[GO:0097029]  
2
  • UniProtKB
  • Ortholog Curator
Negative regulation of chemokine secretiondefinition[GO:0090198]  
1
  • UniProtKB
Negative regulation of JNK cascadedefinition[GO:0046329]  
1
  • UniProtKB
Negative regulation of toll-like receptor 3 signaling pathwaydefinition[GO:0034140]  
1
  • UniProtKB
Negative regulation of tumor necrosis factor-mediated signaling pathwaydefinition[GO:0010804]  
1
  • UniProtKB
Neutrophil activationdefinition[GO:0042119]  
1
  • UniProtKB
Positive regulation of actin filament depolymerizationdefinition[GO:0030836]  
1
  • UniProtKB
Positive regulation of cell migrationdefinition[GO:0030335]  
1
  • Ortholog Curator
Positive regulation of chemotaxisdefinition[GO:0050921]  
1
  • Ortholog Curator
Positive regulation of cytokine secretion involved in immune responsedefinition[GO:0002741]  
1
  • UniProtKB
Positive regulation of cytosolic calcium ion concentrationdefinition[GO:0007204]  
2
  • UniProtKB
  • Ortholog Curator
Positive regulation of eosinophil degranulationdefinition[GO:0043311]  
1
  • UniProtKB
Positive regulation of ERK1 and ERK2 cascadedefinition[GO:0070374]  
2
  • UniProtKB
  • Ortholog Curator
Positive regulation of glomerular filtrationdefinition[GO:0003104]  
1
  • Ortholog Curator
Positive regulation of I-kappaB kinase/NF-kappaB signalingdefinition[GO:0043123]  
1
  • UniProtKB
Positive regulation of interleukin-6 secretiondefinition[GO:2000778]  
2
  • UniProtKB
Positive regulation of interleukin-8 secretiondefinition[GO:2000484]  
4
  • UniProtKB
Positive regulation of JNK cascadedefinition[GO:0046330]  
1
  • UniProtKB
Positive regulation of leukocyte chemotaxisdefinition[GO:0002690]  
1
  • BHF-UCL
Positive regulation of neutrophil mediated killing of gram-negative bacteriumdefinition[GO:0070963]  
1
  • UniProtKB
Positive regulation of phagocytosis, engulfmentdefinition[GO:0060100]  
1
  • UniProtKB
Positive regulation of phosphatidylinositol 3-kinase signalingdefinition[GO:0014068]  
1
  • Ortholog Curator
Positive regulation of positive chemotaxisdefinition[GO:0050927]  
1
  • BHF-UCL
Positive regulation of pseudopodium assemblydefinition[GO:0031274]  
1
  • Ortholog Curator
Positive regulation of renin secretion into blood streamdefinition[GO:1900135]  
1
  • Ortholog Curator
Positive regulation of Rho protein signal transductiondefinition[GO:0035025]  
2
  • UniProtKB
  • Ortholog Curator
Positive regulation of superoxide anion generationdefinition[GO:0032930]  
1
  • UniProtKB
Positive regulation of toll-like receptor 2 signaling pathwaydefinition[GO:0034137]  
1
  • UniProtKB
Positive regulation of toll-like receptor 3 signaling pathwaydefinition[GO:0034141]  
1
  • UniProtKB
Positive regulation of toll-like receptor 4 signaling pathwaydefinition[GO:0034145]  
1
  • UniProtKB
Positive regulation of transcription from RNA polymerase II promoterdefinition[GO:0045944]  
1
  • UniProtKB
Positive regulation of vasodilationdefinition[GO:0045909]  
1
  • Ortholog Curator
Regulation of blood coagulationdefinition[GO:0030193]  
1
  • BHF-UCL
Regulation of I-kappaB kinase/NF-kappaB signalingdefinition[GO:0043122]  
1
  • UniProtKB
Regulation of JNK cascadedefinition[GO:0046328]  
1
  • UniProtKB
T cell activation involved in immune responsedefinition[GO:0002286]  
1
  • Ortholog Curator
Thrombin receptor signaling pathwaydefinition[GO:0070493] silver  
1
  • InterPro 2 GO
Pathways 
According to KEGG, this protein belongs to the following pathways:
African trypanosomiasis  hsa05143+2150  
Neuroactive ligand-receptor interaction  hsa04080+2150  
According to Reactome, this protein belongs to the following pathways:
G alpha (q) signalling events  REACT_18283  
Peptide ligand-binding receptors  REACT_14819  
 

Keywords

Biological process 
Immunity  definition   [KW-0391]
Inflammatory response  definition   [KW-0395]
Innate immunity  definition   [KW-0399]
Molecular function 
G-protein coupled receptor  definition   [KW-0297]
Receptor  definition   [KW-0675]
Transducer  definition   [KW-0807]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

Other
GeneWiki: Protease_activated_receptor_2
GenomeRNAi: 2150
PRO: PR:P55085
Chemistry
GuidetoPHARMACOLOGY: 348